Cadmium is a modern environmental contaminant that is toxic and carcinogenic. Glycyrrhiza glabra is a traditional medicinal herb which grows in the various parts of the World. Recent studies demonstrated that G. glabra has antifungal, antimicrobial, antioxidant, and powerful antiinflammatory features. The purpose of this study was to investigate the genetic safety of extracts from G. glabra and its effects on cadmium (as CdCl2) induced genotoxicity. Therefore we evaluated the capability of G. glabra extract to inhibit the rate of micronucleus (MN), sister chromatid exchange (SCE) formations induced by CdCl2. Moreover, to assess the effects of G. glabra on cell viability and oxidative status, we performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and total antioxidant capacity (TAC) assays. Our results showed that there were significant increases (P < 0.05) in both SCE and MN frequencies of cultures treated with CdCl2 (5 ppm) as compared to controls. However, co-application of G. glabra extract (5, 10 and 20 ppm) and CdCl2 resulted in decreases of MN and SCE rates as compared to the group treated with CdCl2 alone. Again, the results of MTT and TAC assays clearly indicated dose dependent ameliorative effects of G. glabra extracts against CdCl2 toxicity. In conclusion, this study demonstrated for the first time that G. glabra extracts provided increased resistance of DNA against CdCl2 induced genetic and oxidative damage in human lymphocytes. So, the risk on target tissues of CdCl2 could be reduced and ensured early recovery from its toxicity.
Cadmium; Glycyrrhiza glabra; Genotoxicity; Human lymphocytes; Oxidative stress; Protective effect
Present study aimed to evaluate the protective role of the aqueous extract of Phyllanthus niruri (P. niruri) against nimesulide-induced hepatic disoder in mice by determining levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) in serum and also by measuring the hepatic content of the antioxidant enzymes, superoxide dismitase (SOD) and catalase (CAT); the free radical scavenger, reduced glutathione (GSH) and thiobarbituric acid reacting substances (TBARS). Aqueous extract of P. niruri was administered either orally or intraperitoneally in different doses and times as needed for the experiments. Intraperitoneal of the extract (100 mg/kg body weight for seven days) reduced nimesulide (750 mg/kg body weight for 3 days) induced increased levels of GOT (37.0±1.8 units/ml in control group vs. 91.8±2.0 units/ml in nimesulide treated group vs. 35.0±1.0 units/ml in extract treated group), GPT (30.0±2.1 units/ml in control group vs. 88.4±2.9 units/ml in nimesulide treated group vs. 34.1±1.8 units/ml in extract treated group), and ALP (7.86±0.47 KA units/ml in control group vs. 23.80±0.60 KA units/ml in nimesulide treated group vs. 7.30±0.40 KA units/ml, in extract treated group) to almost nomal. In addition, P. niruri restored the nimesulide induced alterations of hepatic SOD (550±20 units/mg total protein in control group vs. 310±13 units/mg total protein in nimesulide treated group vs. 515±10 units/mg total protein in extract treated group), CAT (99.5±2 units/mg total protein in control group vs. 25.0±1.5 units/mg total protein in nimesulide treated group vs. 81.0±0.8 units/mg total protein in extract treated group), GSH (90±3 nmoles/mg total protein in control group vs. 17±4.2 nmoles/mg total protein in nimesulide treated group vs. 81±1 nmoles/mg total protein in extract treated group) and TBARS (measured as MDA, 36.6±3.0 nmoles/g liver tissue in control group vs. 96.3±5.2 nmoles/g liver tissue in nimesulide treated group vs. 41.2±1.7 nmoles/g liver tissue in extract treated group) contents. Dose-dependent studies showed that the herb could protect liver even if the nimesulide-induced injury is severe. Intraperitoneal administration of the extract showed better protective effect than oral administration. Combining all, the data suggest that P. niruri possesses hepatoprotective activity against nimesulide-induced liver toxicity and probably acts via an antioxidant defense mechanism. To the best of our knowledge, this is the first report of the hepatoprotective action of P. niruri against nimesulide induced liver damage.
Nimesulide; oxidative stress; hepatotoxicity; Phyllanthus niruri; antioxidant; hepatoprotection
Rhodiola imbricata is a perennial herb of the family Crassulaceae, which has significant traditional usage as medicine and is also known to biosynthesize phytochemicals such as flavonoids, coumarins and phenyl glycosides. The present investigation was aimed to estimate the hepatoprotective activity of R. imbricata rhizome acetone extract against paracetamol (2 g/kg) induced liver toxicity. Paracetamol was administered to induce hepatic damage in Wistar rats. 200 and 400 mg/kg doses of rhizome acetone extract and silymarin (25 mg/kg) were used as treatment groups. The blood samples were analyzed for biochemical markers of hepatic injury and tissue samples were subjected for estimation of liver antioxidants and histopathological studies. Analysis of the extract treated rats (400 mg/kg) showed an elevation of superoxide dismutase (0.326 units/min/mg protein), catalase (185.03 μmole of H2O2 consumed/min/mg protein), glutothione peroxidase (19.26 mg GSH consumed/min/mg protein) and reduced glutathione (16.2 μmole of GSH/mg protein). Moreover, the biochemical parameters in serum like alkaline phosphatase, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and lipid profiles were also improved in treated groups compared to the control. The oral administration of different doses of rhizome acetone extract significantly protected the hepatic cells from damage. The hematological and biochemical parameters were also normal in extract treated rats compared to the control and standard (silymarin) groups. The HPLC analysis revealed the presence of some important phenolic compounds which could be responsible for the hepatoprotective activity. This study proved that R. imbricata could be taken as a good natural source of the hepatoprotective agent.
Hepatotoxicity; In vivo antioxidants; Histopathology; Hematology; Biochemical markers
Satureja Macrostema is used both as a functional food and as a drug. In this study, the antioxidative potential of the methanol extract of Satureja Macrostema (SM) was evaluated using various antioxidant assays, including DPPH, superoxide, nitric oxide (NO), hydroxyl radical scavenging and iron-chelating activity. Total phenolic and flavonoid content of SM was also determined by a colorimetric method. The extract exhibited powerful free radical scavenging, especially against DPPH, hydroxyl radical scavenging and iron-chelating activity as well as a moderate effect on NO and superoxide anions. The protective effects of methanol extract of SM were studied in carbon tetrachloride-reduced biochemical markers of hepatic injury such as glutamate pyruvate transaminase (SGPT), serum glutamate oxalaoacetate transaminase (SGOT), alkaline phosphatase (ALP), serum bilirubin, cholesterol alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. The increased level of HDL demonstrated dose dependant reduction in the in vivo peroxidation induced by CCl4. SM could protect from paracetamol-induced lipid peroxidation eliminating the deleterious effects of toxic metabolites from paracetamol. Degree of protection was measured by using biochemical parameters such as serum transaminase (GOT and GPT), alkaline phosphatase (ALKP) and bilirubin. Hexane and chloroform extracts did not show any effects. Results obtained in the present study suggest that S. Macrostema elicits hepatoprotectivity through antioxidant activity on carbon tetrachloride- and paracetamol-induced hepatic damage in rats.
Satureja Macrostema; hepatoprotective activity; antioxidant effect; biochemical parameters
It has been reported that dietary polyunsaturated fats (PUFA) increase liver injury in response to ethanol feeding. We tested the hypothesis that diets rich in linoleic acid (18:2n-6) would affect acute liver injury after acetaminophen injection and that protein restriction might exacerbate the liver injury. We examined effects of feeding diets with either 15% (wt/wt) corn oil or 14% beef tallow and 1% corn oil for six weeks with either 6 or 20 g/100 g protein on acute hepatotoxicity. After the feeding period, liver injury was induced by injecting either with 600 mg/kg body weight acetaminophen suspended in gum arabic-based vehicle, or with vehicle alone during fasting status. Samples of liver and plasma were taken for analyses of hepatic glutathione (GSH) levels and liver-specific enzymes [(Glutamate-pyruvate transaminase (GPT) and glutamate-oxaloacetate transaminase (GOT)], respectively. Whereas GSH level was significantly lower in only group fed 15% corn oil with 6 g/100 g protein among acetaminophen-treated groups, activities of GPT and GOT were significantly elevated in all groups except the one fed beef tallow with 20 g/100 g protein, suggesting low protein might exacerbate drug-induced hepatotoxicity. The feeding regimens changed the ratio of 18:2n-6 to oleic acid (18:1n-9) in total liver lipids approximately five-fold, and produced modest changes in arachidonic acid (20:4n-6). We conclude that diets with high 18:2n-6 promote acetaminophen-induced liver injury compared to diets with more saturated fatty acids (SFA). In addition, protein restriction appeared to exacerbate the liver injury.
Fatty acid composition; linoleic acid; saturated fatty acid; acetaminophen; hepatotoxicity
To evaluate the hepatoprotective and antioxidant activity of Clitoria ternatea (C. ternatea) flower extract against acetaminophen-induced liver toxicity.
The antioxidant property of C. ternatea flower extract was investigated by employing established in vitro antioxidant assay. The C. ternatea flower extract was studied in this work for its hepatoprotective effect against acetaminophen-induced liver toxicity in mice. Activity was measured by monitoring the levels of aspartate aminotransferase, alanine aminotransferase, billirubin and glutathione with histopathological analysis.
The amount of total phenolics and flavonoids were estimated to be 105.40±2.47 mg/g gallic acid equivalent and 72.21±0.05 mg/g catechin equivalent respectively. The antioxidant activity of C. ternatea flower extract was 68.9% at a concentration of 1 mg/mL and was also concentration dependant, with an IC50 value of 327.00 µg/mL. The results of acetaminophen-induced liver toxicity experiment showed that mice treated with the extract (200 mg/kg) showed a significant decrease in alanine aminotransferase, aspartate aminotransferase, and bilirubin levels, which were all elevated in the paracetamol group (P<0.05). Meanwhile, the level of glutathione was found to be restored in extract treated animals compared to the groups treated with acetaminophen alone (P<0.05). Therapy of extract also showed its protective effect on histopathological alterations and supported the biochemical finding.
The present work confirmed the hepatoprotective effect of C. ternatea flower against model hepatotoxicant acetaminophen.
Clitoria ternatea flower; Acetaminophen; Hepatoprotective; Antioxidant activity
c-Jun N-terminal kinase (JNK) activation promotes hepatocyte death during acetaminophen overdose, a common cause of drug-induced liver failure. While mitogen-activated protein kinase (MAPK) phosphatase (Mkp)-1 is a critical negative regulator of JNK MAPK, little is known about the role of Mkp-1 during hepatotoxicity. In this study, we evaluated the role of Mkp-1 during acute acetaminophen toxicity. Mkp-1+/+ and Mkp-1−/− mice were dosed ip with vehicle or acetaminophen at 300 mg/kg (for mechanistic studies) or 400 mg/kg (for survival studies). Tissues were collected 1–6 hr post 300 mg/kg dosing to assess glutathione levels, organ damage, and MAPK activation. Mkp-1−/− mice exhibited more rapid plasma clearance of acetaminophen than did Mkp-1+/+ mice, indicated by a quicker decline of plasma acetaminophen level. Moreover, Mkp-1−/− mice suffered more severe liver injury, indicated by higher plasma alanine transaminase activity and more extensive centrilobular apoptosis and necrosis. Hepatic JNK activity in Mkp-1−/− mice was higher than in Mkp-1+/+ mice. Finally, Mkp-1−/− mice displayed a lower overall survival rate and shorter median survival time after dosing with 400 mg/kg acetaminophen. The more severe phenotype exhibited by Mkp-1−/− mice indicates that Mkp-1 plays a protective role during acute acetaminophen overdose, potentially through regulation of JNK.
toxicity; hepatic; mouse; acetaminophen; Mkp-1; JNK
Aim: A polyherbal formulation prepared from a mixture of leaves of Gongronema latifolia, Ocimum gratissimum and Vernonia amygdalina (GOV) was evaluated for hepato-nephro protective properties against acetaminophen-induced toxicity in Wistar albino rats.
Materials and Methods: Normal Wistar albino rats were orally treated with different doses of GOV extract (2, 4 and 8 g/kg b. wt), distilled water and some standard hepatoprotective drugs such as Liv 52 and silymarin for 14 days. However, a day prior to the 14th day, 3 g/kg body weight dose of Acetaminophen (APAP) was administered p.o. 1h before GOV and the standard drugs to induce hepatic and renal damage. The normal control was setup which received only distilled water. The serum levels of liver marker enzymes, biochemical analytes, antioxidant enzymes and hematological parameters were monitored.
Results: The results showed that pretreatment of experimental animals with a different doses of the polyherbal formulation dose dependently caused a significant (p≤0.05) increase in the levels of most of the measured hematological parameters but significantly (p≤0.05) reduced the levels of MCV and monocytes when compared to the APAP induced toxin control group. Rats pretreated with GOV exhibited significant (p < 0.05) increase in serum levels of ALP, ALT, AST, GGT, LDH, Cholesterol, Triglycerides, Urea and a subsequent decrease in Albumin, Creatine and Total protein when compared to the normal rats. This trend in enzyme and biochemical analytes levels were significantly (p < 0.05) reversed when compared to toxin control group. GOV significantly (p < 0.05) and dose dependently increased the serum, kidney and hepatic CAT, GPx, GSH, GST, SOD and total protein activity in APAP induced damage in rats compared to the toxin control groups.
Conclusion: The data from this study suggest that the polyherbal formulation possess hepato and nephron-protective potential against acetaminophen induced hepatotoxicity in rats, thus providing scientific rationale for its use in traditional medicine for the treatment of liver diseases.
Acetaminophen; Antioxidant; Gongronema latifolia; Hepatotoxicity; Liver marker enzymes; Nephron-protective; Ocimum gratissimum; Vernonia amygdalina
The potential biological functions of A. nilotica have long been described in traditional system of medicine. However, the protective effect of A. nilotica on acetaminophen-induced hepatotoxicity is still unknown. The present study attempted to investigate the protective effect of A. nilotica against acetaminophen-induced hepatic damage in Wistar rats. The biochemical liver functional tests Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP), total bilirubin, total protein, oxidative stress test (Lipid peroxidation), antioxidant parameter glutathione (GSH), and histopathological changes were examined. Our results show that the pretreatment with A. nilotica (250 mg/kg·bw) orally revealed attenuation of serum activities of ALT, AST, ALP, liver weight, and total bilirubin levels that were enhanced by administration of acetaminophen. Further, pretreatment with extract elevated the total protein and GSH level and decreased the level of LPO. Histopathological analysis confirmed the alleviation of liver damage and reduced lesions caused by acetaminophen. The present study undoubtedly provides a proof that hepatoprotective action of A. nilotica extract may rely on its effect on reducing the oxidative stress in acetaminophen-induced hepatic damage in rat model.
Arecoline is a major alkaloid of areca nuts which are widely chewed by southeast Asian and it manifests various toxic effects in different organs of human and animals. In this work, mature mice were treated by vitamins C plus E, arecoline, or both daily for four weeks. The results showed that arecoline significantly increased the levels of serum alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and significantly decreased the levels of reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) in the liver tissues. Additionally, the body weight, testis weight, sperm counts, motility and normal sperms also were significantly decreased. The supplement of vitamins C and E can bring the activities of ALP and GPT to normal levels and partially restore the sperm counts compared to the arecoline-treated group but have no other positive effects. In conclusion, the vitamins C and E partially attenuated the arecoline-induced hepatotoxiciy but basically had on protective effects against the arecoline-induced testicular toxicity.
Arecoline; Hepatotoxicity; Protective effects; Testicular toxicity; Vitamins C and E
Honey, a supersaturated natural product of honey bees, contains complex compounds with antioxidant properties and therefore has a wide a range of applications in both traditional and modern medicine. In the present study, the protective effects of Sundarban honey from Bangladesh against acetaminophen- (APAP-) induced hepatotoxicity and nephrotoxicity in experimental rats were investigated. Adult male Wistar rats were pretreated with honey (5 g/kg) for 4 weeks, followed by the induction of hepatotoxicity and nephrotoxicity via the oral administration of a single dose of APAP (2 g/kg). Organ damage was confirmed by measuring the elevation of serum alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), total protein (TP), total bilirubin (TB), urea, creatinine, and malondialdehyde (MDA). Histopathological alterations observed in the livers and the kidneys further confirmed oxidative damage to these tissues. Animals pretreated with Sundarban honey showed significantly markedly reduced levels of all of the investigated parameters. In addition, Sundarban honey ameliorated the altered hepatic and renal morphology in APAP-treated rats. Overall, our findings indicate that Sundarban honey protects against APAP-induced acute hepatic and renal damage, which could be attributed to the honey's antioxidant properties.
The hepatoprotective activity of a fraction of the leaf extract of A.indica against carbon tetrachloride : liquid paraffin (1:1) induced liver damage in rats at doses of 100 mg/kg and 200 mg/kg was evaluated. A significant dose dependent hepatoprotective activity was evidenced by lowering of the elevated levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), acid phosphatase (ACP) and alkaline phosphatase (ALP) in the serum of CCl4 : liquid paraffin (1:1) treated rats.
This investigation was undertaken to evaluate ethanolic extract of Cordia macleodii leaves for possible antioxidant and hepatoprotective potential. Antioxidant activity of the extracts was evaluated by four established, in vitro methods viz. 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging method, nitric oxide (NO) radical scavenging method, iron chelation method and reducing power method. The extract demonstrated a significant dose dependent antioxidant activity comparable with ascorbic acid. The extract was also evaluated for hepatoprotective activity by carbon tetrachloride (CCl4) induced liver damage model in rats. CCl4 produced a significant increase in levels of serum glutamate pyruvate transaminase (GPT), serum glutamate oxaloacetate transaminase (GOT), Alkaline Phosphatase (ALP) and total bilirubin. Pretreatment of the rats with ethanolic extract of C. macleodii (100, 200 and 400 mg/kg po) inhibited the increase in levels of GPT, GOT, ALP and total bilirubin and the inhibition was comparable with Silymarin (100 mg/kg po). The present study revealed that C. macleodii leaves have significant radical scavenging and hepatoprotective activities.
Antioxidant; Hepatoprotective; Cordia macleodii; DPPH; Nitric oxide
A decoction comprised of Nigella sativa seeds, Hemidesmus indicus root and Smilax glabra rhizome is used to treat cancer patients in Sri Lanka. However, the anti-carcinogenic properties of this decoction have not been experimentally confirmed. The purpose of this study was to determine whether the above decoction could protect against chemically induce hepatocarcinogenesis.
The effects of this decoction on diethylnitrosamine (DEN) induced hepatocarcinogenesis were examined in male Wistar rats using the medium term bioassay system of Ito, based on a 2-step model of hepatocarcinogenesis. Rats were randomly divided into 6 groups of 10 each. Groups 1 to 4 were injected with DEN (200 mg/kg) to initiate carcinogenesis. Twenty-four hours later groups 1 and 2 were administered the decoction at 4 g/kg body weight/day (dose 1) and 6 g/kg body weight/day (dose 2), respectively. Group 3 and group 4 were given distilled water instead of the decoction and a suspension of garlic powder (20 g/kg body weight/day) in distilled water (positive control), respectively. Group 5 and 6 were injected with normal saline and twenty-four hours later group 5 was given distilled water (normal control) while group 6 was given decoction dose 2 (decoction control). Oral feeding continued for two weeks after which all rats were subjected to 2/3 partial hepatectomy to promote carcinogenesis. Oral feeding continued for eight more weeks. At the end of the 10th week, rats were sacrificed and samples of livers taken for immunohistochemical studies.
Carcinogenic potential was scored by comparing the number, area and staining intensity of glutathione S-transferase placental form (GST-P) positive foci and the number of cells/cm2 of the positive foci in the livers of the six groups of rats.
The number and area of DEN-mediated GST-P positive foci, number of cells/cm2 of foci and staining intensity of the foci were significantly (P > 0.001) reduced by the decoction and garlic in the order dose 2 = garlic >dose 1.
Overall results indicate that the decoction comprised of N. sativa, S. glabra and H. indicus has the potential to protect rat liver against DEN induced hepatocarcinogenesis
To investigate the hepatoprotective activity of methanolic leaf extract of Cyathea gigantea (C. gigantea) against paracetamol induced liver damage in rats.
The hepatoprotective activity for plant extract was investigated for paracetamol induced hepatoxicity in rats. Wistar albino rats of either sex were divided into five groups of 6 animals each and are given orally the following treatment for seven days. The normal control group was given 1% Na.CMC 1 mL/kg bw, p.o. Paracetamol at dose of 1 g/kg bw, p.o. was given as toxic dose for inducing hepatotoxicity. Silymarin (50 mg/kg, p.o.) was given as reference standard. Two doses of C. gigantea extract i.e., 100 mg/kg, p.o. and 200 mg/kg, p.o. were tested for hepatoprotective activity. The treatment was given for seven days and after 24 h of last treatment blood was collected from retro-orbital plexus and analysed for various serum parameters like serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), total bilirubin (TB) and total protein (TP) in different groups.
The paracetamol intoxication lead to histological and biochemical deteriorations. The treatment with methanolic leaf extract of C. gigantea reduced the elevated levels of SGOT, SGPT, ALP, TB and also reversed the hepatic damage towards normal which further supports the hepatoprotective activity of leaf extract of C. gigantea.
The methanolic extract of leaves of C. gigantea at doses of 100 mg/kg bw and 200 mg/kg bw have significant effect on liver of paracetamol induced hepatotoxicity model in rats.
Hepatoprotective; Cyathea gigantea; Paracetamol; Silymarin; Hepatotoxicity
The genus Amaranthus has potential activity as a hepatoprotective agent.
The present pharmacological investigation focuses on evaluation of the efficacy of aqueous extract of roots of Amaranthus tricolor Linn. for their protection against paracetamol (PCM) overdose induced hepatotoxicity.
Materials and Methods:
The aqueous extract of roots of A. tricolor Linn. was prepared and phytochemical screening was done. The biochemical investigation viz. serum glutamic oxaloacetate transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), alkaline phosphatase (ALP) and total Bilirubin (TB) was done against PCM-induced hepatotoxicity in wistar albino rats. The histopathological studies of liver were also done.
The phytochemical screening of the aqueous extract showed the presence of alkaloids, carbohydrates, flavanoids, amino acids, proteins, fixed oil, saponins and tannins, and phenolic compounds. Pretreatment with the aqueous extract of root significantly prevented the physical, biochemical, histological, and functional changes induced by paracetamol in the liver. The extract showed significant hepatoprotective effects as evidenced by decreased serum enzyme activities like SGPT, SGOT, ALP, and TB, which was supported by histopathological studies of liver. The aqueous extract showed significant hepatoprotective activity comparable with standard drug silymarin as well as hepatotoxin drug PCM.
From these results, it is concluded that the A. tricolor has potential effectiveness in treating liver damage in a dose dependent manner.
Amaranthaceae; Amaranthus tricolor Linn.; aqueous extract; hepatoprotective activity; paracetamol
Hepatotoxicity caused by acetaminophen can be prevented by enzyme-catalyzed conjugation of its reactive metabolite with glutathione (GSH). Since we have shown in previous studies that 6-N-propyl-2-thiouracil (PTU) can substitute for GSH as a substrate for the GSH S-transferases, we examined the possibility that PTU might also protect against acetaminophen hepatotoxicity by direct chemical interaction with the reactive metabolite of acetaminophen. In an in vitro system consisting of [3H]acetaminophen, liver microsomes from phenobarbital-pretreated rats, and an NADPH-generating system, we found that PTU had a dose-dependent additive effect with GSH on inhibition of acetaminophen covalent binding. PTU administration also resulted in a dose-dependent decrease in both GSH depletion and covalent binding in vivo in acetaminophen-treated mice. To examine the possible mechanisms by which PTU exerts its protective effect, we studied the action of PTU on both acetaminophen conjugation and metabolic activation. PTU had no effect upon acetaminophen pharmacokinetics in phenobarbital-pretreated rats, as examined by measuring acetaminophen concentration in bile, urine, and blood after an intraperitoneal dose, nor did it alter the total amount of polar conjugates formed. Microsomes from PTU-treated rats were unaltered in cytochrome P-450 concentrations and p-nitroanisole-O-demethylase, benzo-α-pyrene hydroxylase, and cytochrome c-reductase activities. Furthermore PTU did not decrease acetaminophen-GSH adduct formation in vitro, suggesting that there was no reduction in drug activation. However, in bile from [35S]PTU and [3H]acetaminophen treated rats, as well as in incubates of the two drugs with liver microsomes, a new 35S- and 3H-containing product could be identified. By both thin layer chromatography and high pressure liquid chromatography this new product, which co-eluted with [3H]acetaminophen, was separated from unreacted [35S]PTU. The formation of this product in vitro was a function of PTU concentration and reached a maximum of 0.06 μmol/min per mg protein at 0.5 mM PTU. In vivo, the total biliary excretion of this product over 4 h (116 nmol) equaled the net reduction in acetaminophen metabolite covalent binding in the liver of phenobarbital-pretreated rats (108 nmol). We conclude that PTU, independent of its antithyroid effect, diminishes hepatic macromolecular covalent binding of acetaminophen reactive metabolite both in vivo and in vitro, and it does so by detoxifying the reactive metabolite through direct chemical interaction in a manner similar to GSH. These observations may define the mechanism by which PTU is protective against liver injury caused by acetaminophen.
This study evaluated the effect of gamma irradiation on the reduction of the toxicity of mistletoe lectin using both in vitro and in vivo models. To extract the lectin from mistletoe, an (NH4)2SO4 precipitation method was employed and the precipitant purified using a Sepharose 4B column to obtain the pure lectin fraction. Purified lectin was then gamma-irradiated at doses of 0, 5, 10, 15, and 20 kGy, or heated at 100 °C for 30 min. Toxic effects of non-irradiated, irradiated, and heat-treated lectins were tested using hemagglutination assays, cytotoxicity assays, hepatotoxicity, and a mouse survival test and immunological response was tested using cytokine production activity. Hemagglutination of lectin was remarkably decreased (P < 0.05) by irradiation at doses exceeding 10 kGy and with heat treatment. However, lectin irradiated with 5 kGy maintained its hemagglutination activity. The cytotoxicity of lectin was decreased by irradiation at doses over 5 kGy and with heat treatment. In experiments using mouse model, glutamate oxaloacetate transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels were decreased in the group treated with the 5 kGy irradiated and heat-treated lectins as compared to the intact lectin, and it was also shown that 5 kGy irradiated and heat-treated lectins did not cause damage in liver tissue or mortality. In the result of immunological response, tumor necrosis factor (TNF-α) and interleukin (IL-6) levels were significantly (P < 0.05) increased in the 5 kGy gamma-irradiated lectin treated group. These results indicate that 5 kGy irradiated lectin still maintained the immunological response with reduction of toxicity. Therefore, gamma-irradiation may be an effective method for reducing the toxicity of lectin maintaining the immune response.
▸ Cytotoxicity of lectin against immune cells was decreased by gamma-irradiation at doses above 5 kGy. ▸ The liver toxicity of gamma-irradiated lectin (5 kGy) was decreased, as shown by levels of GOT and GPT. ▸ Gamma-irradiated lectin (5 kGy) was not lethal for mice. ▸ Gamma-irradiated lectin (5 kGy) still maintained immunological responses.
Mistletoe lectin; Toxicity; Gamma irradiation; Immune response; Cytotoxicity; Cytokine
Chrysanthemum indicum L. flower (CIF) has been widely used as tea in Korea. This study aims to investigate the hepatoprotective effect of the hot water extract of CIF (HCIF) in in vitro and in vivo systems.
Hepatoprotective activities were evaluated at 250 to 1000 μg/mL concentrations by an in vitro assay using normal human hepatocytes (Chang cell) and hepatocellular carcinoma cells (HepG2) against CCl4-induced cytotoxicity. Cytochrome P450 2E1, which is a key indicator of hepatic injury, was detected by western blot analysis using rabbit polyclonal anti-human CYP2E1 antibody. An in vivo hepatoprotective activity assay was performed at 1000 to 4000 μg/mL concentrations on CCl4-induced acute toxicity in rats, and the serum levels of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were determined by standard enzyme assays.
The hepatoprotective effects of HCIF significantly reduced the levels of GOT (60.1%, P = 0.000) and GPT (64.5%, P = 0.000) compared with the vehicle control group (CCl4 alone). The survival rates of HepG2 and Chang cells were significantly improved compared with the control group [82.1% (P = 0.034) and 62.3% (P = 0.002), respectively]. HCIF [50 mg/kg body weight (BW)] treatment significantly reduced the serum levels of GOT (49.5%, P = 0.00), GPT (55.5%, P = 0.00), ALP (30.8%, P = 0.000) and LDH (45.6%, P = 0.000) compared with the control group in this in vivo study. The expression level of cytochrome P450 2E1 (CYP2E1) protein was also significantly decreased at the same concentration (50 mg/kg BW; P = 0.018).
HCIF inhibited bioactivation of CCl4-induced hepatotoxicity and downregulates CYP2E1 expression in vitro and in vivo.
Rats fed with hypercholesterolemic diet showed a significant increase in serum total—cholesterol, liver homogenate total-cholesterol, HDL-cholesterol and changed LDL-cholesterol, and HDL/LDL ratio in comparison to control. Flaxseedchutney (FC) supplemented diet (15%, w/w) was found to be more effective in restoring lipid profile changes in rats fed with cholesterol, (1.0%). The activities of serum marker enzymes glutamate oxaloacetate transminase (GOT), glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) were elevated significantly in carbon tetrachloride induced rats. Administration of flaxseedchutney (15%, w/w) resulted in depletion of serum marker enzymes and exhibited recoupment thus showing significant hepatoprotective effect. It was observed that flaxseedchutney supplemented diet could lower the serum cholesterol and as a potential source of antioxidants it could exert protection against hepatotoxic damage induced by carbon tetrachloride (CCl4) in rats.
Flaxseedchutney; Carbon tetrachloride; Hypocholesterolemic effect; Hepatoprotective effect
The present study was designed to evaluate the influence of α-lipoic acid treatment in rats exposed to malathion. Forty adult male rats were used in this study and distributed into four groups. Animals of group 1 were untreated and served as control. Rats of group 2 were orally given malathion at a dose level of 100 mg/kg body weight (BW) for a period of one month. Experimental animals of group 3 were orally given α-lipoic acid at a dose level of 20 mg/kg BW and after 3 hours exposed to malathion at the same dose given to group 2. Rats of group 4 were supplemented with α-lipoic acid at the same dose given to group 3. The activities of serum glutamic oxaloacetic acid transaminase (GOT), glutamic pyruvic acid transaminase (GPT), alkaline phosphatase (ALP), and acid phosphatase (ACP), and the values of creatinine, urea, and uric acid were statistically increased, while the values of total protein and total albumin were significantly decreased in rats exposed to malathion. Moreover, administration of malathion for one month resulted in damage of liver and kidney structures. Administration of α-lipoic acid before malathion exposure to rat can prevent severe alterations of hematobiochemical parameters and disruptions of liver and kidney structures. In conclusion, this study obviously demonstrated that pretreatment with α-lipoic acid significantly attenuated the physiological and histopathological alterations induced by malathion. Also, the present study identifies new areas of research for development of better therapeutic agents for liver, kidney, and other organs' dysfunctions and diseases.
Trichosanthes lobata (family cucurbitaceae) is used to treat malarial fever and liver disorders. This study aims to investigate possible hepatoprotective activities of ethanolic extract of Trichosanthes lobata against paracetamol-induced hepatotoxicity.
Hepatotoxicity was induced in Wistar male rats by oral administration, 2 g/kg body weight on 7th day after the administration of ethanolic extract of Trichosanthes lobata and silymarin (100 mg/kg). Ethanolic extract of Trichosanthes lobata was administered orally at doses of 200 mg/kg and 400 mg/kg body weight daily for 7 days. Several serum markers, aspartate transaminase, alanine transaminase, alkaline phosphatase, bilirubin, total protein was measured to assess the effect of the extract on paracetamol (acetaminophen)-induced hepatic damage. The study included histopathological examination of liver sections.
Blood samples from rats treated with ethanolic extract of Trichosanthes lobata (200 mg/kg body weight and 400 mg/kg body weight) had significant reductions in serum markers in paracetamol administered animals, indicating the effect of the extract in restoring the normal functional ability of hepatocytes. Silymarin (100 mg/kg, p.o.) was used as a reference drug.
The ethanolic extract of Trichosanthes lobata exhibits protective effects against paracetamol‒induced hepatotoxicity.
Protective effects of Houttuynia cordata aqueous extract (HCAE) against acetaminophen-induced hepatotoxicity in Balb/cA mice were examined.
HCAE, at 1 or 2 g/L, was added into the drinking water for 4 weeks. Acute liver injury was induced by acetaminophen treatment intraperitoneally (350 mg/kg body weight).
Acetaminophen treatment significantly depleted hepatic glutathione (GSH) content, increased hepatic malonyldialdehyde (MDA), reactive oxygen species (ROS) and oxidized glutathione (GSSG) levels, and decreased hepatic activity of glutathione peroxidase (GPX), catalase and superoxide dismutase (SOD) (p<0.05). The pre-intake of HCAE alleviated acetaminophen-induced oxidative stress by retaining GSH content, decreasing MDA, ROS and GSSG production, and maintaining activity of GPX, catalase and SOD in liver (p<0.05). The pre-intake of HCAE also significantly lowered acetaminophen-induced increase in cytochrome P450 2E1 activity (p<0.05). Acetaminophen treatment increased hepatic release of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein-1 (p<0.05). HCAE intake significantly diminished acetaminophen-induced elevation of these cytokines (p<0.05).
These results support that HCAE could provide hepato-protection
Hepatotoxicity; Houttuynia cordata; Acetaminophen; MCP-1; CYP2E1
The chemopreventive effects of certain phytoconstituents can be exploited for their use as functional foods, dietary supplements and even as drugs. The natural compounds, acting as anti-genotoxic and free radical scavenging compounds, may serve as potent chemopreventive agents. These can inhibit DNA modulatory activities of mutagens and help preventing pathological processes.
Present study on Glycyrrhiza glabra L., a promising medicinal plant, widely used in traditional medicine, focused on the bioassay-guided fractionation of its extracts for the isolation of certain phytochemicals with anti-genotoxic potential against oxidative mutagens.
Materials and Methods:
The methanol extract of Glycyrrhiza glabra rhizomes was subjected to column chromatography, and isolated fraction was evaluated for its anti-genotoxic and antioxidant potential using SOS chromotest, Comet assay, and DPPH radical scavenging assay.
GLG fraction, which was characterized as Glycyrrhizic acid, inhibited the genotoxicity of oxidative mutagens viz., H2O2 and 4NQOquite efficiently. In SOS chromotest, using E.coli PQ37 tester strain, it inhibited induction factor induced by H2O2 and 4NQO by 75.54% and 71.69% at the concentration of 121.46 μM,respectively. In Comet assay, it reduced the tail moment induced by H2O2 and 4NQO by 70.21% and 69.04%, respectively, at the same concentration in human blood lymphocytes. The isolated fraction also exhibited DPPH free radical scavenging activity and was able to scavenge 85.95% radicals at a concentration of 120 μM.
Glycyrrhizic acid is a potential modulator of genotoxins as well as efficient scavenger of free radicals.
Chemoprevention; Glycyrrhiza glabra L.; glycyrrhizic acid; H2O2; oxidative mutagens; 4NQO
Hepatoprotective activity of the roots of Decalepis hamiltonii (Wight and Arn) was studied using carbon tetrachloride (CCl4) induced liver injury model in albino rats. The hepatotoxicity produced by acute CCl4 administration was found to be inhibited by pretreating the rats with crude methanolic extract of the roots of D. hamiltonii (Dh) prior to CCl4 induction. Hepatotoxic inhibition was measured with the decreased levels of hepatic serum marker enzymes (glutamate-pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) and lipid peroxide formation. Imbalance level of glutathione (GSH) and antioxidant enzymes such as catalase, glutathione peroxidase, and glutathione reductase were normalized in rats pretreated with Dh extract followed by CCl4 administration. Pathological changes of hepatic lesions caused by CCl4 were also improved by pretreatment with the Dh root extract. The results of this study indicate that roots of D. hamiltonii could afford a significant protective action in the alleviation of CCl4-induced hepatic damage in rats.
Antioxidant activity; CCl4; Decalepis hamiltonii; hepatoprotective